| First Author | Riascos-Bernal DF | Year | 2017 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 37 |
| Issue | 5 | Pages | 879-888 |
| PubMed ID | 28302627 | Mgi Jnum | J:263668 |
| Mgi Id | MGI:6162601 | Doi | 10.1161/ATVBAHA.116.308643 |
| Citation | Riascos-Bernal DF, et al. (2017) Inhibition of Smooth Muscle beta-Catenin Hinders Neointima Formation After Vascular Injury. Arterioscler Thromb Vasc Biol 37(5):879-888 |
| abstractText | OBJECTIVE: Smooth muscle cells (SMCs) contribute to neointima formation after vascular injury. Although beta-catenin expression is induced after injury, whether its function is essential in SMCs for neointimal growth is unknown. Moreover, although inhibitors of beta-catenin have been developed, their effects on SMC growth have not been tested. We assessed the requirement for SMC beta-catenin in short-term vascular homeostasis and in response to arterial injury and investigated the effects of beta-catenin inhibitors on vascular SMC growth. APPROACH AND RESULTS: We used an inducible, conditional genetic deletion of beta-catenin in SMCs of adult mice. Uninjured arteries from adult mice lacking SMC beta-catenin were indistinguishable from controls in terms of structure and SMC marker gene expression. After carotid artery ligation, however, vessels from mice lacking SMC beta-catenin developed smaller neointimas, with lower neointimal cell proliferation and increased apoptosis. SMCs lacking beta-catenin showed decreased mRNA expression of Mmp2, Mmp9, Sphk1, and S1pr1 (genes that promote neointima formation), higher levels of Jag1 and Gja1 (genes that inhibit neointima formation), decreased Mmp2 protein expression and secretion, and reduced cell invasion in vitro. Moreover, beta-catenin inhibitors PKF118-310 and ICG-001 limited growth of mouse and human vascular SMCs in a dose-dependent manner. CONCLUSIONS: SMC beta-catenin is dispensable for maintenance of the structure and state of differentiation of uninjured adult arteries, but is required for neointima formation after vascular injury. Pharmacological beta-catenin inhibitors hinder growth of human vascular SMCs. Thus, inhibiting beta-catenin has potential as a therapy to limit SMC accumulation and vascular obstruction. |
